There are two major innovative aspects to our proposal: 1) To develop magnetic resonance imaging (MRI) as a means to monitor and predict functional recovery after traumatic brain injury (TBI);and 2) To treat TBI with bone marrow stromal cells (MSCs) early, i.e. within 24 hours of injury, as a neuroprotective and neurorestorative therapy. Neurorestorative treatment of TBI using MSCs has demonstrated promise in promoting neuronal remodeling, and improvement of functional recovery. However, we and others have not studied the beneficial effects of early, within 24 hours of injury, treatment with MSCs. Also, there is a compelling need to noninvasively monitor brain remodeling and functional recovery and to translate these methodologies from experimental studies to the clinic. We propose that MRI can sensitively monitor ongoing structural remodeling of brain tissue after TBI that reflects neurological function, and therefore, MRI can be employed to assess recovery and ultimately be applied to the TBI patient. In this proposal, we will develop and implement MR methodologies to investigate the effects of early and late MSC treatment on the migration and distribution of MSCs and lesion volume after TBI (Aim 1), neurite reorganization (Aim 2), and the relationship between brain remodeling and functional recovery (Aim 3) in the experimental animal subjected to TBI. MRI measurements of brain remodeling will be verified using three dimensional laser scanning confocal microscopy and immuno-histochemistry. Neurological outcome will be assessed using a battery of behavioral tests. With these novel approaches, we expect that MRI methodologies for measurement of distribution and concentration of MSCs and neurite reorganization are valid new tools for monitoring the recovery from TBI after restorative therapy. These methods should lead to optimization of treatment protocols and improved management of recovery from TBI. PUBLIC HEALTH RELEVANCE: The investigation of early MSC therapy of TBI utilizing MR-measures of brain neurite reorganization and bone marrow stromal cell (MSC) distribution for predicting brain functional recovery after traumatic brain injury (TBI) and could promise new patient therapies aimed at improving TBI recovery. These studies have the potential to greatly enhance neurological outcomes from TBI and to noninvasively monitor the associated neurite reorganization leading to the recovery of functions.